Abstract
Aims: To determine risk for central nervous system/autonomic nervous system (CNS/ANS) signs following in utero cocaine and opiate exposure.
Methods: A multisite study was designed to determine outcomes of in utero cocaine and opiate exposure. A total of 11 811 maternal/infant dyads were enrolled. Drug exposed (EXP) infants were identified by maternal self report of cocaine or opiate use or by meconium testing. Of 1185 EXP, meconium analysis confirmed exposure in 717 to cocaine (CO) only, 100 to opiates (OP), and 92 to opiates plus cocaine (OP+CO); 276 had insufficient or no meconium to confirm maternal self report. Negative exposure history was confirmed in 7442 by meconium analysis and unconfirmed in 3184. Examiners masked to exposure status, assessed each enrolled infant. Using generalised estimating equations, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated for manifesting a constellation of CNS/ANS outcomes and for each sign associated with cocaine and opiate exposure.
Results: Prevalence of CNS/ANS signs was low in CO, and highest in OP+CO. Signs were significantly related to one another. After controlling for confounders, CO was associated with increased risk of manifesting a constellation of CNS/ANS outcomes, OR (95% CI): 1.7 (1.2 to 2.2), independent of OP effect, OR (95% CI): 2.8 (2.1 to 3.7). OP+CO had additive effects, OR (95% CI): 4.8 (2.9 to 7.9). Smoking also increased the risk for the constellation of CNS/ANS signs, OR (95% CI) of 1.3 (1.04 to 1.55) and 1.4 (1.2 to 1.6), respectively, for use of less than half a pack per day and half a pack per day or more.
Conclusion: Cocaine or opiate exposure increases the risk for manifesting a constellation of CNS/ANS outcomes.
Full Text
The Full Text of this article is available as a PDF (173.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ballard J. L., Khoury J. C., Wedig K., Wang L., Eilers-Walsman B. L., Lipp R. New Ballard Score, expanded to include extremely premature infants. J Pediatr. 1991 Sep;119(3):417–423. doi: 10.1016/s0022-3476(05)82056-6. [DOI] [PubMed] [Google Scholar]
- Bauer Charles R., Shankaran Seetha, Bada Henrietta S., Lester Barry, Wright Linda L., Krause-Steinrauf Heidi, Smeriglio Vincent L., Finnegan Loretta P., Maza Penelope L., Verter Joel. The Maternal Lifestyle Study: drug exposure during pregnancy and short-term maternal outcomes. Am J Obstet Gynecol. 2002 Mar;186(3):487–495. doi: 10.1067/mob.2002.121073. [DOI] [PubMed] [Google Scholar]
- Bingol N., Fuchs M., Diaz V., Stone R. K., Gromisch D. S. Teratogenicity of cocaine in humans. J Pediatr. 1987 Jan;110(1):93–96. doi: 10.1016/s0022-3476(87)80297-4. [DOI] [PubMed] [Google Scholar]
- Chasnoff I. J., Burns W. J., Schnoll S. H., Burns K. A. Cocaine use in pregnancy. N Engl J Med. 1985 Sep 12;313(11):666–669. doi: 10.1056/NEJM198509123131105. [DOI] [PubMed] [Google Scholar]
- Cherukuri R., Minkoff H., Feldman J., Parekh A., Glass L. A cohort study of alkaloidal cocaine ("crack") in pregnancy. Obstet Gynecol. 1988 Aug;72(2):147–151. [PubMed] [Google Scholar]
- Chiriboga C. A., Bateman D. A., Brust J. C., Hauser W. A. Neurologic findings in neonates with intrauterine cocaine exposure. Pediatr Neurol. 1993 Mar-Apr;9(2):115–119. doi: 10.1016/0887-8994(93)90045-e. [DOI] [PubMed] [Google Scholar]
- Chiriboga C. A., Brust J. C., Bateman D., Hauser W. A. Dose-response effect of fetal cocaine exposure on newborn neurologic function. Pediatrics. 1999 Jan;103(1):79–85. doi: 10.1542/peds.103.1.79. [DOI] [PubMed] [Google Scholar]
- Chiriboga C. A., Vibbert M., Malouf R., Suarez M. S., Abrams E. J., Heagarty M. C., Brust J. C., Hauser W. A. Neurological correlates of fetal cocaine exposure: transient hypertonia of infancy and early childhood. Pediatrics. 1995 Dec;96(6):1070–1077. [PubMed] [Google Scholar]
- Coles C. D., Platzman K. A., Smith I., James M. E., Falek A. Effects of cocaine and alcohol use in pregnancy on neonatal growth and neurobehavioral status. Neurotoxicol Teratol. 1992 Jan-Feb;14(1):23–33. doi: 10.1016/0892-0362(92)90025-6. [DOI] [PubMed] [Google Scholar]
- Datta-Bhutada S., Johnson H. L., Rosen T. S. Intrauterine cocaine and crack exposure: neonatal outcome. J Perinatol. 1998 May-Jun;18(3):183–188. [PubMed] [Google Scholar]
- Dempsey D. A., Hajnal B. L., Partridge J. C., Jacobson S. N., Good W., Jones R. T., Ferriero D. M. Tone abnormalities are associated with maternal cigarette smoking during pregnancy in in utero cocaine-exposed infants. Pediatrics. 2000 Jul;106(1 Pt 1):79–85. doi: 10.1542/peds.106.1.79. [DOI] [PubMed] [Google Scholar]
- Dixon S. D., Bejar R. Echoencephalographic findings in neonates associated with maternal cocaine and methamphetamine use: incidence and clinical correlates. J Pediatr. 1989 Nov;115(5 Pt 1):770–778. doi: 10.1016/s0022-3476(89)80661-4. [DOI] [PubMed] [Google Scholar]
- Doberczak T. M., Shanzer S., Senie R. T., Kandall S. R. Neonatal neurologic and electroencephalographic effects of intrauterine cocaine exposure. J Pediatr. 1988 Aug;113(2):354–358. doi: 10.1016/s0022-3476(88)80283-x. [DOI] [PubMed] [Google Scholar]
- ElSohly M. A., Stanford D. F., Murphy T. P., Lester B. M., Wright L. L., Smeriglio V. L., Verter J., Bauer C. R., Shankaran S., Bada H. S. Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium. J Anal Toxicol. 1999 Oct;23(6):436–445. doi: 10.1093/jat/23.6.436. [DOI] [PubMed] [Google Scholar]
- Farrar H. C., Kearns G. L. Cocaine: clinical pharmacology and toxicology. J Pediatr. 1989 Nov;115(5 Pt 1):665–675. doi: 10.1016/s0022-3476(89)80640-7. [DOI] [PubMed] [Google Scholar]
- Fitzmaurice G. M., Laird N. M., Zahner G. E., Daskalakis C. Bivariate logistic regression analysis of childhood psychopathology ratings using multiple informants. Am J Epidemiol. 1995 Dec 1;142(11):1194–1203. doi: 10.1093/oxfordjournals.aje.a117578. [DOI] [PubMed] [Google Scholar]
- Fricker H. S., Segal S. Narcotic addiction, pregnancy, and the newborn. Am J Dis Child. 1978 Apr;132(4):360–366. doi: 10.1001/archpedi.1978.02120290032004. [DOI] [PubMed] [Google Scholar]
- Fried P. A. Cigarettes and marijuana: are there measurable long-term neurobehavioral teratogenic effects? Neurotoxicology. 1989 Fall;10(3):577–583. [PubMed] [Google Scholar]
- Fulroth R., Phillips B., Durand D. J. Perinatal outcome of infants exposed to cocaine and/or heroin in utero. Am J Dis Child. 1989 Aug;143(8):905–910. doi: 10.1001/archpedi.1989.02150200057018. [DOI] [PubMed] [Google Scholar]
- Hadeed A. J., Siegel S. R. Maternal cocaine use during pregnancy: effect on the newborn infant. Pediatrics. 1989 Aug;84(2):205–210. [PubMed] [Google Scholar]
- Heier L. A., Carpanzano C. R., Mast J., Brill P. W., Winchester P., Deck M. D. Maternal cocaine abuse: the spectrum of radiologic abnormalities in the neonatal CNS. AJNR Am J Neuroradiol. 1991 Sep-Oct;12(5):951–956. [PMC free article] [PubMed] [Google Scholar]
- Kandall S. R., Gartner L. M. Late presentation of drug withdrawal symptoms in newborns. Am J Dis Child. 1974 Jan;127(1):58–61. doi: 10.1001/archpedi.1974.02110200060008. [DOI] [PubMed] [Google Scholar]
- Katikaneni Lakshmi D., Salle Floyd R., Hulsey Thomas C. Neonatal hair analysis for benzoylecgonine: a sensitive and semiquantitative biological marker for chronic gestational cocaine exposure. Biol Neonate. 2002 Jan;81(1):29–37. doi: 10.1159/000047181. [DOI] [PubMed] [Google Scholar]
- Kramer L. D., Locke G. E., Ogunyemi A., Nelson L. Neonatal cocaine-related seizures. J Child Neurol. 1990 Jan;5(1):60–64. doi: 10.1177/088307389000500115. [DOI] [PubMed] [Google Scholar]
- LeBlanc P. E., Parekh A. J., Naso B., Glass L. Effects of intrauterine exposure to alkaloidal cocaine ('crack') Am J Dis Child. 1987 Sep;141(9):937–938. doi: 10.1001/archpedi.1987.04460090014001. [DOI] [PubMed] [Google Scholar]
- Lester B. M., Corwin M. J., Sepkoski C., Seifer R., Peucker M., McLaughlin S., Golub H. L. Neurobehavioral syndromes in cocaine-exposed newborn infants. Child Dev. 1991 Aug;62(4):694–705. doi: 10.1111/j.1467-8624.1991.tb01563.x. [DOI] [PubMed] [Google Scholar]
- Madden J. D., Payne T. F., Miller S. Maternal cocaine abuse and effect on the newborn. Pediatrics. 1986 Feb;77(2):209–211. [PubMed] [Google Scholar]
- Martin J. C., Barr H. M., Martin D. C., Streissguth A. P. Neonatal neurobehavioral outcome following prenatal exposure to cocaine. Neurotoxicol Teratol. 1996 Nov-Dec;18(6):617–625. doi: 10.1016/s0892-0362(96)00131-6. [DOI] [PubMed] [Google Scholar]
- Mayes L. C., Carroll K. M. Neonatal withdrawal syndrome in infants exposed to cocaine and methadone. Subst Use Misuse. 1996 Jan;31(2):241–253. doi: 10.3109/10826089609045811. [DOI] [PubMed] [Google Scholar]
- Napiorkowski B., Lester B. M., Freier M. C., Brunner S., Dietz L., Nadra A., Oh W. Effects of in utero substance exposure on infant neurobehavior. Pediatrics. 1996 Jul;98(1):71–75. [PubMed] [Google Scholar]
- Neerhof M. G., MacGregor S. N., Retzky S. S., Sullivan T. P. Cocaine abuse during pregnancy: peripartum prevalence and perinatal outcome. Am J Obstet Gynecol. 1989 Sep;161(3):633–638. doi: 10.1016/0002-9378(89)90368-2. [DOI] [PubMed] [Google Scholar]
- Nestler E. J., Aghajanian G. K. Molecular and cellular basis of addiction. Science. 1997 Oct 3;278(5335):58–63. doi: 10.1126/science.278.5335.58. [DOI] [PubMed] [Google Scholar]
- Neuspiel D. R., Hamel S. C. Cocaine and infant behavior. J Dev Behav Pediatr. 1991 Feb;12(1):55–64. [PubMed] [Google Scholar]
- Oro A. S., Dixon S. D. Perinatal cocaine and methamphetamine exposure: maternal and neonatal correlates. J Pediatr. 1987 Oct;111(4):571–578. doi: 10.1016/s0022-3476(87)80125-7. [DOI] [PubMed] [Google Scholar]
- Ostrea E. M., Chavez C. J., Strauss M. E. A study of factors that influence the severity of neonatal narcotic withdrawal. J Pediatr. 1976 Apr;88(4 Pt 1):642–645. doi: 10.1016/s0022-3476(76)80027-3. [DOI] [PubMed] [Google Scholar]
- Pane M. A., Traystman R. J., Gleason C. A. Ecgonine methyl ester, a major cocaine metabolite, causes cerebral vasodilation in neonatal sheep. Pediatr Res. 1997 Jun;41(6):815–821. doi: 10.1203/00006450-199706000-00005. [DOI] [PubMed] [Google Scholar]
- Preis O., Choi S. J., Rudolph N. Pentazocine withdrawal syndrome in the newborn infant. Am J Obstet Gynecol. 1977 Jan 15;127(2):205–206. doi: 10.1016/s0002-9378(16)33256-2. [DOI] [PubMed] [Google Scholar]
- Prenner B. M. Neonatal withdrawal syndrome associated with hydroxyzine hydrochloride. Am J Dis Child. 1977 May;131(5):529–530. doi: 10.1001/archpedi.1977.02120180043007. [DOI] [PubMed] [Google Scholar]
- Rajegowda B. K., Glass L., Evans H. E., Masó G., Swartz D. P., Leblanc W. Methadone withdrawal in newborn infants. J Pediatr. 1972 Sep;81(3):532–534. doi: 10.1016/s0022-3476(72)80181-1. [DOI] [PubMed] [Google Scholar]
- Richardson G. A., Hamel S. C., Goldschmidt L., Day N. L. The effects of prenatal cocaine use on neonatal neurobehavioral status. Neurotoxicol Teratol. 1996 Sep-Oct;18(5):519–528. doi: 10.1016/0892-0362(96)00062-1. [DOI] [PubMed] [Google Scholar]
- Rosen T. S., Pippenger C. E. Pharmacologic observations on the neonatal withdrawal syndrome. J Pediatr. 1976 Jun;88(6):1044–1048. doi: 10.1016/s0022-3476(76)81074-8. [DOI] [PubMed] [Google Scholar]
- Rothstein P., Gould J. B. Born with a habit. Infants of drug-addicted mothers. Pediatr Clin North Am. 1974 May;21(2):307–321. [PubMed] [Google Scholar]
- Schulman C. A. Alterations of the sleep cycle in heroin-addicted and "suspect" newborns. Neuropadiatrie. 1969 Jun-Jul;1(1):89–100. doi: 10.1055/s-0028-1091866. [DOI] [PubMed] [Google Scholar]
- Slotkin T. A. Fetal nicotine or cocaine exposure: which one is worse? J Pharmacol Exp Ther. 1998 Jun;285(3):931–945. [PubMed] [Google Scholar]
- Tronick E. Z., Frank D. A., Cabral H., Mirochnick M., Zuckerman B. Late dose-response effects of prenatal cocaine exposure on newborn neurobehavioral performance. Pediatrics. 1996 Jul;98(1):76–83. [PMC free article] [PubMed] [Google Scholar]
- Tsay C. H., Partridge J. C., Villarreal S. F., Good W. V., Ferriero D. M. Neurologic and ophthalmologic findings in children exposed to cocaine in utero. J Child Neurol. 1996 Jan;11(1):25–30. doi: 10.1177/088307389601100106. [DOI] [PubMed] [Google Scholar]
- Tyson H. K. Neonatal withdrawal symptoms associated with maternal use of propoxyphene hydrochloride (Darvon). J Pediatr. 1974 Nov;85(5):684–685. doi: 10.1016/s0022-3476(74)80519-6. [DOI] [PubMed] [Google Scholar]
- Webster P. A. Withdrawal symptoms in neonates associated with maternal antidepressant therapy. Lancet. 1973 Aug 11;2(7824):318–319. doi: 10.1016/s0140-6736(73)90815-5. [DOI] [PubMed] [Google Scholar]
- Wiggins R. C. Pharmacokinetics of cocaine in pregnancy and effects on fetal maturation. Clin Pharmacokinet. 1992 Feb;22(2):85–93. doi: 10.2165/00003088-199222020-00001. [DOI] [PubMed] [Google Scholar]
- Wilson G. S., Desmond M. M., Verniaud W. M. Early development of infants of heroin-addicted mothers. Am J Dis Child. 1973 Oct;126(4):457–462. doi: 10.1001/archpedi.1973.02110190381004. [DOI] [PubMed] [Google Scholar]
- Wilson G. S., Desmond M. M., Wait R. B. Follow-up of methadone-treated and untreated narcotic-dependent women and their infants: health, developmental, and social implications. J Pediatr. 1981 May;98(5):716–722. doi: 10.1016/s0022-3476(81)80830-x. [DOI] [PubMed] [Google Scholar]
- Woods N. S., Eyler F. D., Conlon M., Behnke M., Wobie K. Pygmalion in the cradle: observer bias against cocaine-exposed infants. J Dev Behav Pediatr. 1998 Aug;19(4):283–285. doi: 10.1097/00004703-199808000-00007. [DOI] [PubMed] [Google Scholar]
- Young S. L., Vosper H. J., Phillips S. A. Cocaine: its effects on maternal and child health. Pharmacotherapy. 1992;12(1):2–17. [PubMed] [Google Scholar]
- Zelson C., Lee S. J., Casalino M. Neonatal narcotic addiction. Comparative effects of maternal intake of heroin and methadone. N Engl J Med. 1973 Dec 6;289(23):1216–1220. doi: 10.1056/NEJM197312062892303. [DOI] [PubMed] [Google Scholar]
- Zelson C., Rubio E., Wasserman E. Neonatal narcotic addiction: 10 year observation. Pediatrics. 1971 Aug;48(2):178–189. [PubMed] [Google Scholar]
- Zuckerman B., Amaro H., Cabral H. Validity of self-reporting of marijuana and cocaine use among pregnant adolescents. J Pediatr. 1989 Nov;115(5 Pt 1):812–815. doi: 10.1016/s0022-3476(89)80668-7. [DOI] [PubMed] [Google Scholar]
- Zuckerman B., Frank D. A., Hingson R., Amaro H., Levenson S. M., Kayne H., Parker S., Vinci R., Aboagye K., Fried L. E. Effects of maternal marijuana and cocaine use on fetal growth. N Engl J Med. 1989 Mar 23;320(12):762–768. doi: 10.1056/NEJM198903233201203. [DOI] [PubMed] [Google Scholar]
- van Baar A. L., Fleury P., Soepatmi S., Ultee C. A., Wesselman P. J. Neonatal behavior after drug dependent pregnancy. Arch Dis Child. 1989 Feb;64(2):235–240. doi: 10.1136/adc.64.2.235. [DOI] [PMC free article] [PubMed] [Google Scholar]